Role of charge and hydrophobicity in liprotide formation: a molecular dynamics study with experimental constraints

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Role of charge and hydrophobicity in liprotide formation : a molecular dynamics study with experimental constraints. / Nedergaard Pedersen, Jannik; Wilhelmus Johannes Maria Frederix, Pim; Skov Pedersen, Jan; Marrink, Siewert Jan; Otzen, Daniel.

In: ChemBioChem, Vol. 19, No. 3, 02.02.2018, p. 263–271.

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Nedergaard Pedersen, Jannik ; Wilhelmus Johannes Maria Frederix, Pim ; Skov Pedersen, Jan ; Marrink, Siewert Jan ; Otzen, Daniel. / Role of charge and hydrophobicity in liprotide formation : a molecular dynamics study with experimental constraints. In: ChemBioChem. 2018 ; Vol. 19, No. 3. pp. 263–271.

Bibtex

@article{3a7cf45efdee4d439e60ee97d34f2a4d,
title = "Role of charge and hydrophobicity in liprotide formation: a molecular dynamics study with experimental constraints",
abstract = "Bovine α-lactalbumin (aLA) and oleate (OA) form a complex that has been intensively studied for its tumoricidal activity. Small-angle X-ray scattering (SAXS) has revealed a lipid core surrounded by partially unfolded protein. We call this type of complex a liprotide. Little is known of the molecular interactions between OA and aLA and no technique has so far provided any high resolution structure of liprotides. Here, we used coarse grained (CG) molecular dynamics (MD) simulations, Isothermal titration calorimetry (ITC) and SAXS to investigate the interactions between aLA and OA during the process of liprotide formation. By using ITC we found that the strongest enthalpic interactions occurred at a molar ratio of 12.0 ± 1.4 OA/aLA. Liprotides formed between OA and aLA at several OA/aLA ratios in silico were stable in both CG and all-atom simulations. We have calculated SAXS spectra from the simulated structures which show good agreement with experimentally measured patterns of matching liprotides. The simulations showed that aLA assumes a molten globular (MG) state, exposing several hydrophobic patches involved in interactions with OA. Initial binding of aLA to OA occurs in an area of aLA where a high amount of positive charge is located and only later hydrophobic interactions become important. Our findings suggest a general mechanism for liprotide formation and may explain the ability of a large number of proteins to form liprotides with OA.",
keywords = "Journal Article",
author = "{Nedergaard Pedersen}, Jannik and {Wilhelmus Johannes Maria Frederix}, Pim and {Skov Pedersen}, Jan and Marrink, {Siewert Jan} and Daniel Otzen",
note = "{\circledC} 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",
year = "2018",
month = "2",
day = "2",
doi = "10.1002/cbic.201700496",
language = "English",
volume = "19",
pages = "263–271",
journal = "ChemBioChem",
issn = "1439-4227",
publisher = "Wiley - V C H Verlag GmbH & Co. KGaA",
number = "3",

}

RIS

TY - JOUR

T1 - Role of charge and hydrophobicity in liprotide formation

T2 - a molecular dynamics study with experimental constraints

AU - Nedergaard Pedersen, Jannik

AU - Wilhelmus Johannes Maria Frederix, Pim

AU - Skov Pedersen, Jan

AU - Marrink, Siewert Jan

AU - Otzen, Daniel

N1 - © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PY - 2018/2/2

Y1 - 2018/2/2

N2 - Bovine α-lactalbumin (aLA) and oleate (OA) form a complex that has been intensively studied for its tumoricidal activity. Small-angle X-ray scattering (SAXS) has revealed a lipid core surrounded by partially unfolded protein. We call this type of complex a liprotide. Little is known of the molecular interactions between OA and aLA and no technique has so far provided any high resolution structure of liprotides. Here, we used coarse grained (CG) molecular dynamics (MD) simulations, Isothermal titration calorimetry (ITC) and SAXS to investigate the interactions between aLA and OA during the process of liprotide formation. By using ITC we found that the strongest enthalpic interactions occurred at a molar ratio of 12.0 ± 1.4 OA/aLA. Liprotides formed between OA and aLA at several OA/aLA ratios in silico were stable in both CG and all-atom simulations. We have calculated SAXS spectra from the simulated structures which show good agreement with experimentally measured patterns of matching liprotides. The simulations showed that aLA assumes a molten globular (MG) state, exposing several hydrophobic patches involved in interactions with OA. Initial binding of aLA to OA occurs in an area of aLA where a high amount of positive charge is located and only later hydrophobic interactions become important. Our findings suggest a general mechanism for liprotide formation and may explain the ability of a large number of proteins to form liprotides with OA.

AB - Bovine α-lactalbumin (aLA) and oleate (OA) form a complex that has been intensively studied for its tumoricidal activity. Small-angle X-ray scattering (SAXS) has revealed a lipid core surrounded by partially unfolded protein. We call this type of complex a liprotide. Little is known of the molecular interactions between OA and aLA and no technique has so far provided any high resolution structure of liprotides. Here, we used coarse grained (CG) molecular dynamics (MD) simulations, Isothermal titration calorimetry (ITC) and SAXS to investigate the interactions between aLA and OA during the process of liprotide formation. By using ITC we found that the strongest enthalpic interactions occurred at a molar ratio of 12.0 ± 1.4 OA/aLA. Liprotides formed between OA and aLA at several OA/aLA ratios in silico were stable in both CG and all-atom simulations. We have calculated SAXS spectra from the simulated structures which show good agreement with experimentally measured patterns of matching liprotides. The simulations showed that aLA assumes a molten globular (MG) state, exposing several hydrophobic patches involved in interactions with OA. Initial binding of aLA to OA occurs in an area of aLA where a high amount of positive charge is located and only later hydrophobic interactions become important. Our findings suggest a general mechanism for liprotide formation and may explain the ability of a large number of proteins to form liprotides with OA.

KW - Journal Article

U2 - 10.1002/cbic.201700496

DO - 10.1002/cbic.201700496

M3 - Journal article

C2 - 29156084

VL - 19

SP - 263

EP - 271

JO - ChemBioChem

JF - ChemBioChem

SN - 1439-4227

IS - 3

ER -